Collagen remodeling in breast cancer progression: from molecular mechanisms to diagnostic and therapeutic opportunities.

Collagen remodeling is an emerging hallmark of breast cancer progression, offering profound insights into tumor biology and therapeutic vulnerability. While breast cancer has long been understood through the lens of genetic mutations and cellular deregulation, recent advances have emphasized the crucial role of the tumor microenvironment (TME), particularly the extracellular matrix (ECM), in directing cancer progression. As the most prevalent structural protein within the ECM, collagen plays a key role in tissue mechanics, cell signaling, and immune regulation. This review examines the current understanding of the molecular configuration and diversity of collagen types found in breast tissue, with an emphasis on the pathological alterations that occur during malignant transformation. We explore how enzymes, such as matrix metalloproteinases (MMPs) and lysyl oxidase (LOX), regulate collagen degradation and crosslinking. These processes drive ECM stiffening and the formation of aligned collagen fibers, which promote tumor invasion, angiogenesis, and immune evasion. This article also highlights tumor-associated collagen signatures (TACS) as potential diagnostic biomarkers and evaluates advanced imaging modalities, including techniques like second harmonic generation (SHG) microscopy and magnetic resonance elastography (MRE), which enable in vivo assessment of collagen remodeling. Furthermore, we review therapeutic approaches targeting collagen-modifying enzymes and emerging nanoparticle-based delivery systems designed to disrupt the fibrotic ECM and improve drug penetration. Ultimately, collagen is now recognized not merely as a structural scaffold, but as an influential factor actively involved in the progression of breast cancer. Understanding the mechanisms and clinical implications of collagen remodeling may open novel paths for personalized diagnostics and targeted therapies, offering new hope for the management of aggressive and treatment-resistant breast cancers.